tbuckley/cabot-search huggingface dataset:
The probiotic <i>Bacillus subtilis</i> BS50 decreases gastrointestinal symptoms in healthy adults: a randomized, double-blind, placebo-controlled trial
Authors: Sean M. Garvey, Eunice Mah, Traci M. Blonquist, Valerie N. Kaden, Jessica L. Spears
Journal: Gut Microbes (2022)

Durable spore-forming probiotics are increasingly formulated into foods, beverages, and dietary supplements. To help meet this demand, the safety and efficacy of daily supplementation of Bacillus subtilis BS50 for 6 weeks was investigated in a randomized, double-blind, placebo-controlled, parallel clinical trial of 76 healthy adults. Before and during supplementation, gastrointestinal symptoms were recorded daily using a multi-symptom questionnaire. Clinical chemistry, hematology, plasma lipids, and intestinal permeability and inflammation markers were measured at baseline and end of study. Compared to placebo, 2 × 109 colony-forming units (CFU) BS50 per day increased the proportion of participants showing improvement from baseline to week 6 in the composite score for bloating, burping, and flatulence (47.4% vs. 22.2%), whereby the odds of detecting an improvement were higher with BS50 (OR [95% CI]: 3.2 [1.1, 8.7], p = .024). Analyses of individual gastrointestinal symptoms indicate that BS50 increased the proportion of participants showing an improvement at week 6 compared to placebo for burping (44.7% vs. 22.2%, p = .041) and bloating (31.6% vs. 13.9%, p = .071), without affecting other symptoms. There were no clinically meaningful changes in clinical chemistry, hematology, plasma lipids and intestinal permeability and other inflammation markers. In conclusion, the results suggest that dietary supplementation of 2 × 109 CFU Bacillus subtilis BS50 per day is a well-tolerated and safe strategy to alleviate gas-related gastrointestinal symptoms in healthy adults.Abbreviations AE adverse event; BHD bowel habits diary; BMI body mass index; BSS Bristol Stool Scale; CFU colony-forming unit; CRP C-reactive protein; FGID functional gastrointestinal disorder; GI gastrointestinal; GITQ Gastrointestinal Tolerance Questionnaire; GLP-1 glucagon-like peptide 1; GSRS Gastrointestinal Symptom Rating Scale; HDL-C high-density lipoprotein-cholesterol; IBS irritable bowel syndrome; IL-10 interleukin-10; ITT intent-to-treat; LBP lipopolysaccharide binding protein; LDL-C low-density lipoprotein-cholesterol; PP per protocol; PYY peptide YY; TG triglyceride; total-C total cholesterol
Epidemiology of acute flaccid myelitis in children in the Netherlands, 2014 to 2019
Authors: Jelte Helfferich, Marit MA de Lange, Kimberley SM Benschop, Bart C Jacobs, Coretta C Van Leer-Buter, Adam Meijer, Dewi P Bakker, Eva de Bie, Hilde MH Braakman, Rick Brandsma, Rinze F Neuteboom, Erik H Niks, Jikke-Mien Niermeijer, Vincent Roelfsema, Niels Schoenmaker, Lilian T Sie, Hubert G Niesters, Oebele F Brouwer, Margreet JM te Wierik
Journal: Eurosurveillance (2022)

Background Acute flaccid myelitis (AFM) is a polio-like condition affecting mainly children and involving the central nervous system (CNS). AFM has been associated with different non-polio-enteroviruses (EVs), in particular EV-D68 and EV-A71. Reliable incidence rates in European countries are not available. Aim To report AFM incidence in children in the Netherlands and its occurrence relative to EV-D68 and EV-A71 detections. Methods In 10 Dutch hospitals, we reviewed electronic health records of patients diagnosed with a clinical syndrome including limb weakness and/or CNS infection and who were &lt; 18 years old when symptoms started. After excluding those with a clear alternative diagnosis to AFM, those without weakness, and removing duplicate records, only patients diagnosed in January 2014–December 2019 were retained and further classified according to current diagnostic criteria. Incidence rates were based on definite and probable AFM cases. Cases’ occurrences during the study period were co-examined with laboratory-surveillance detections of EV-D68 and EV-A71. Results Among 143 patients included, eight were classified as definite and three as probable AFM. AFM mean incidence rate was 0.06/100,000 children/year (95% CI: −0.03 to 0.14). All patient samples were negative for EV-A71. Of respiratory samples in seven patients, five were EV-D68 positive. AFM cases clustered in periods with increased EV-D68 and EV-A71 detections. Conclusions AFM is rare in children in the Netherlands. The temporal coincidence of EV-D68 circulation and AFM and the detection of this virus in several cases’ samples support its association with AFM. Increased AFM awareness among clinicians, adequate diagnostics and case registration matter to monitor the incidence.
Fostering Resilience to Very Preterm Birth Through the Caregiving Environment
Authors: Trecia A. Wouldes
Journal: JAMA Network Open (2022)

Mia A. McLean, PhD; Olivia C. Scoten, Bsc, Hons; Cecil M. Y. Chau, Msc; Anne Synnes, MDCM, MHSc; Steven P. Miller, MDCM, MAS; Ruth E. Grunau, PhD
Analysis of US County Characteristics and Clinicians With Waivers to Prescribe Buprenorphine After Changes in Federal Education Requirements
Authors: Thuy Nguyen, Barbara Andraka-Christou, Camila Arnaudo, W. David Bradford, Kosali Simon, Joanne Spetz
Journal: JAMA Network Open (2022)

This cross-sectional study investigates the growth in the number of clinicians in the US who obtained waivers for prescribing buprenorphine after the elimination of federal educational requirements.
Airway epithelial cell-specific delivery of lipid nanoparticles loading siRNA for asthma treatment
Authors: Mengjun Zhang, Huiyang Jiang, Lan Wu, Haoyu Lu, Hriday Bera, Xing Zhao, Xiong Guo, Xulu Liu, Dongmei Cun, Mingshi Yang
Journal: Journal of Controlled Release (2022)
Perspectives of Historically Black College and University Advisors to Premedical Students During the COVID-19 Pandemic
Authors: Jasmine Weiss, Louisa Holaday, Danya Keene, Ngozi D. Akingbesote, Lilanthi Balasuriya, Mona Sharifi, Darin Latimore, Inginia Genao
Journal: JAMA Network Open (2022)

Importance Black students remain underrepresented in medicine despite national efforts to increase diversity in the physician workforce. Historically Black College and University (HBCU) students play a vital role in increasing representation in the workforce. Currently, there is a paucity of literature understanding the impact of COVID-19 on premedical students from HBCUs. Understanding the adverse impact of the pandemic on HBCU students is essential to inform strategies that promote holistic medical school admissions and increased diversity, equity, and inclusion in the medical workforce. Objective To explore premedical advisors' perspectives on the impact of the COVID-19 pandemic on HBCU premedical students pursuing admission to medical school. Design, Setting, and Participants In this qualitative study, semistructured interviews of HBCU premedical advisors were performed from March 2020 to March 2021. One-on-one interviews were conducted with 21 advisors with a depth of experience as advisors, varied educational backgrounds, and diverse geographic representation. Data analysis was performed from March 2021 to December 2021. Main Outcomes and Measures The experiences of HBCU premedical students during the COVID-19 pandemic from the perspective of the premedical advisor. Results Among the 21 participants, 13 (62%) were female, 15 (71%) were Black or African American, 11 (52%) had a doctorate degree, and 7 (33%) had more than 10 years of experience as advisors. Participants described 3 major themes: (1) balancing academic responsibilities with family demands; (2) distraction, disruption, and isolation in the virtual learning environment; and (3) harmful impact of new stressors for HBCU applicants in the medical school admissions process. Conclusions and Relevance In this qualitative study of HBCU advisors to premedical students, advisors described how the COVID-19 pandemic adversely affected undergraduate HBCU premedical students; students faced family hardships, challenges with virtual learning, and uncertainty in the medical school admissions process. These findings suggest that medical schools should continue to create direct interventions to address the challenges that HBCU students faced during the height of the pandemic and as longitudinal consequences of the pandemic. Addressing these issues may improve physician workforce representation and promote more equitable patient care for underserved communities disproportionately affected by COVID-19 and other health disparities.
Association of Symptoms After COVID-19 Vaccination With Anti–SARS-CoV-2 Antibody Response in the Framingham Heart Study
Authors: Emilia A. Hermann, Benjamin Lee, Pallavi P. Balte, Vanessa Xanthakis, Beth D. Kirkpatrick, Mary Cushman, Elizabeth Oelsner
Journal: JAMA Network Open (2022)

This cohort study examines the association of self-reported postvaccination symptoms with anti–SARS-CoV-2 antibody response among Framingham Heart Study participants contributing to the Collaborative Cohort of Cohorts for COVID-19 Research study.
Association of Neonatal Pain-Related Stress and Parent Interaction With Internalizing Behaviors Across 1.5, 3.0, 4.5, and 8.0 Years in Children Born Very Preterm
Authors: Mia A. McLean, Olivia C. Scoten, Cecil M. Y. Chau, Anne Synnes, Steven P. Miller, Ruth E. Grunau
Journal: JAMA Network Open (2022)

Internalizing (anxiety and/or depressive) behaviors are prevalent in children born very preterm (24-32 weeks' gestation). Procedural pain-related stress in the neonatal intensive care unit (NICU) is associated with long-term internalizing problems in this population; however, whether positive parenting during toddlerhood attenuates development of internalizing behaviors across childhood is unknown.To investigate whether neonatal pain-related stress is associated with trajectories of internalizing behaviors across 1.5, 3.0, 4.5, and 8.0 years, and whether supportive parenting behaviors and lower parenting stress at 1.5 and 3.0 years attenuate this association.In this prospective longitudinal cohort study, preterm neonates (born at 24-32 weeks' gestation) were recruited from August 16, 2006, to September 9, 2013, with follow-up visits at ages 1.5, 3.0, 4.5, and 8.0 years. The study was conducted at BC Women's Hospital, Vancouver, Canada, with recruitment from a level III neonatal intensive care unit and sequential developmental assessments performed in a Neonatal Follow-up Program. Data analysis was performed from August to December 2021.Parental report of child internalizing behaviors on the Child Behavior Checklist at 1.5, 3.0, 4.5, and 8.0 years.A total of 234 neonates were recruited, and 186 children (101 boys [54%]) were included in the current study across ages 1.5 (159 children), 3.0 (169 children), 4.5 (162 children), and 8.0 (153 children) years. After accounting for clinical factors associated with prematurity, greater neonatal pain-related stress was associated with more internalizing behaviors across ages (B = 4.95; 95% CI, 0.76 to 9.14). Higher parenting stress at age 1.5 years (B = 0.17; 95% CI, 0.11 to 0.23) and a less supportive parent environment (less sensitivity, structure, nonintrusiveness, nonhostility, and higher parenting stress; B = -5.47; 95% CI, -9.44 to -1.51) at 3.0 years were associated with greater internalizing problems across development to age 8.0 years.In this cohort study of children born very preterm, exposure to repetitive neonatal pain-related stress was associated with persistent internalizing behavior problems across toddlerhood to age 8.0 years. Supportive parenting behaviors during early childhood were associated with better long-term behavioral outcomes, whereas elevated parenting stress was associated with more child anxiety and/or depressive behaviors in this population. These findings reinforce the need to prevent pain in preterm neonates and inform future development of targeted parent-led behavioral interventions.
Immediate Postpartum Long-Acting Reversible Contraception: An Effective and Underutilized Strategy
Authors: Maryam Guiahi
Journal: JAMA Network Open (2022)

An innovative strategy to help reduce the rate of unintended short interval pregnancies (pregnancies that occur within 18 months of delivery) has been the introduction of immediate postpartum longacting reversible contraception (IPP-LARC).IPP-LARC is the provision of either an implant or intrauterine device after delivery and in the hospital setting prior to inpatient discharge.This approach ensures access to the most effective reversible contraceptive options available.Implementing IPP-LARC also addresses the low rate of attendance at outpatient postpartum visits and lack of insurance coverage that Medicaid recipients often face in the postpartum period and thereby serves as an effective health equity strategy.Initially, some state Medicaid agencies offered this option, but with a payment model that included coverage within the global fixed delivery reimbursement.This payment model led to ongoing barriers to implementing IPP-LARC given hospital reluctances to cover the high upfront costs of LARC devices.
A circulating subset of iNKT cells mediates antitumor and antiviral immunity
Authors: Guangwei Cui, Akihiro Shimba, Jianshi Jin, Taisaku Ogawa, Yukiko Muramoto, Hitoshi Miyachi, Shinya Abe, Takuma Asahi, Shizue Tani-ichi, Johannes M. Dijkstra, Yayoi Iwamoto, Kirill Kryukov, Yuanbo Zhu, Daichi Takami, Takahiro Hara, Satsuki Kitano, Yan Xu, Hajime Morita, Moyu Zhang, Lynn Zreka, Keishi Miyata, Takashi Kanaya, Shinya Okumura, Takashi Ito, Etsuro Hatano, Yoshimasa Takahashi, Hiroshi Watarai, Yuichi Oike, Tadashi Imanishi, Hiroshi Ohno, Toshiaki Ohteki, Nagahiro Minato, Masato Kubo, Georg A. Holländer, Hideki Ueno, Takeshi Noda, Katsuyuki Shiroguchi, Koichi Ikuta
Journal: Science Immunology (2022)

Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244-CXCR6-), C1 (CD244-CXCR6+), or C2 (CD244+CXCR6+) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-γ and granzymes and exhibited more NK cell-like features, whereas C1 iNKT cells showed more T cell-like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244+CXCR6+ iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell-like properties distinct from conventional tissue-resident iNKT cells.
The ZFP36 family of RNA binding proteins regulates homeostatic and autoreactive T cell responses
Authors: Melissa E. Cook, Tara R. Bradstreet, Ashlee M. Webber, Jongshin Kim, Andrea Santeford, Kevin M. Harris, Maegan K. Murphy, Jennifer Tran, Nada M. Abdalla, Elizabeth A. Schwarzkopf, Suellen C. Greco, Carmen M. Halabi, Rajendra S. Apte, Perry J. Blackshear, Brian T. Edelson
Journal: Science Immunology (2022)

RNA binding proteins are important regulators of T cell activation, proliferation, and cytokine production. The zinc finger protein 36 (ZFP36) family genes (
When I use a word . . . . Too much healthcare—Biomarkers
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

A biomarker is a biological observation that substitutes for and ideally predicts a clinically relevant endpoint or intermediate outcome that is more difficult to observe. Biomarkers are used in screening for diseases; characterising diseases; ruling out, diagnosing, staging, and monitoring diseases; informing prognoses; individualising therapeutic interventions; predicting adverse drug reactions; predicting and guiding treatment of drug toxicity; identifying cell types (e.g. histological markers); individualising and optimising dosage requirements (genetic biomarkers); and in various aspects of drug discovery and development—as targets for screening compounds, as endpoints for studies of pharmacodynamics and pharmacokinetic/pharmacodynamic relationships, in studying the relationship between the concentration or dose of a drug and its effects, in defining the adverse effects of drug development candidates, in measuring efficacy in clinical trials, and in postmarketing surveillance. Clinical biomarkers are simpler and less expensive to measure than final clinical endpoints and can be analysed repeatedly and over a shorter period of time. However, problems can arise if they are overused or not used properly. Failure or errors in interpretation can occur in the absence of a thorough understanding of the pathophysiology of the disease, the mechanisms of action of the interventions that cause benefits and harms, and confounding factors that can act in parallel.
Defining measures of kidney function in observational studies using routine health care data: methodological and reporting considerations
Authors: Juan Jesus Carrero, Edouard L. Fu, Søren V. Vestergaard, Simon Kok Jensen, Alessandro Gasparini, Viyaasan Mahalingasivam, Samira Bell, Henrik Birn, Uffe Heide-Jørgensen, Catherine M. Clase, Faye Cleary, Josef Coresh, Friedo W. Dekker, Ron T. Gansevoort, Brenda R. Hemmelgarn, Kitty J. Jager, Tazeen H. Jafar, Csaba P. Kovesdy, Manish M. Sood, Bénédicte Stengel, Christian F. Christiansen, Masao Iwagami, Dorothea Nitsch
Journal: Kidney International (2022)

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data.
Mechanisms of CD40-dependent cDC1 licensing beyond costimulation
Authors: Renee Wu, Ray A. Ohara, Suin Jo, Tian-Tian Liu, Stephen T. Ferris, Feiya Ou, Sunkyung Kim, Derek J. Theisen, David A. Anderson, Brian W. Wong, Timothy Gershon, Robert D. Schreiber, Theresa L. Murphy, Kenneth M. Murphy
Journal: Nature Immunology (2022)
Shared and distinct biological circuits in effector, memory and exhausted CD8+ T cells revealed by temporal single-cell transcriptomics and epigenetics
Authors: Josephine R. Giles, Shin Foong Ngiow, Sasikanth Manne, Amy E. Baxter, Omar Khan, Ping Wang, Ryan Staupe, Mohamed S. Abdel-Hakeem, Hua Huang, Divij Mathew, Mark M. Painter, Jennifer E. Wu, Yinghui Jane Huang, Rishi R. Goel, Patrick K. Yan, Giorgos C. Karakousis, Xiaowei Xu, Tara C. Mitchell, Alexander C. Huang, E. John Wherry
Journal: Nature Immunology (2022)
IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation
Authors: Xinhui Ni, Yi Xu, Wang Wang, Baida Kong, Jian Ouyang, Jiwei Chen, Man Yan, Yawei Wu, Qi Chen, Xinxin Wang, Hongquan Li, Xiaoguang Gao, Hongquan Guo, Lian Cui, Zeyu Chen, Yuling Shi, Ronghui Zhu, Wei Li, Tieliu Shi, Lin-Fa Wang, Jinling Huang, Chen Dong, Yuping Lai
Journal: Nature Immunology (2022)

Abstract Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 ( Ddx5 ∆KC ) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93–p38 MAPK–AKT–SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5 ∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.
Interleukin-33-activated neuropeptide CGRP-producing memory Th2 cells cooperate with somatosensory neurons to induce conjunctival itch
Authors: Mikiko Okano, Kiyoshi Hirahara, Masahiro Kiuchi, Miki Onoue, Chiaki Iwamura, Kota Kokubo, Takahisa Hishiya, Yuki Morimoto, Yuzuru Ikehara, Akira Murakami, Nobuyuki Ebihara, Toshinori Nakayama
Journal: Immunity (2022)
CMTM4 is a subunit of the IL-17 receptor and mediates autoimmune pathology
Authors: Daniela Knizkova, Michaela Pribikova, Helena Draberova, Tereza Semberova, Tijana Trivic, Alzbeta Synackova, Andrea Ujevic, Jana Stefanovic, Ales Drobek, Martina Huranova, Veronika Niederlova, Oksana Tsyklauri, Ales Neuwirth, Jolana Tureckova, Ondrej Stepanek, Peter Draber
Journal: Nature Immunology (2022)

Abstract Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C to mediate its stability, glycosylation and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17R signaling complex. Accordingly, CMTM4-deficient mice had a severe defect in the recruitment of immune cells following IL-17A administration and were largely resistant to experimental psoriasis, but not to experimental autoimmune encephalomyelitis. Collectively, our data identified CMTM4 as an essential component of IL-17R and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.